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Steroids. 1997 Jan;62(1):5-9.

Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: a central role for steroidogenic factor 1.

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  • 1Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia 19104, USA.

Erratum in

  • Steroids 1997 Apr;62(4):395.

Abstract

Steroidogenic acute regulatory protein (StAR) plays a critical role in regulating the rate-limiting step in steroid hormone synthesis, cholesterol side-chain cleavage. StAR gene expression is transcriptionally controlled in the gonads by gonadotropic hormones via a cAMP second message. We have begun to analyze factors responsible for the transcriptional activation of the StAR gene. The human StAR gene promoter has at least two cis elements that govern basal and cAMP-regulated gene expression. One of these elements (the distal element) is a consensus binding sequence for the orphan nuclear receptor transcription factor, steroidogenic factor 1 (SF-1); the other (the proximal element) is a related motif. The human StAR promoter is not active in BeWo choriocarcinoma cells, but is functional and cAMP-responsive in murine Y1 adrenal cortical tumor cells. Cotransfection of a plasmid expressing SF-1 allows a StAR promoter construct to function in BeWo cells. Other orphan nuclear transcription factors do not support StAR promoter function in BeWo cell hosts. Deletion or mutation of the distal and proximal cis elements individually substantially reduces SF-1-supported StAR promoter activity. The distal site binds SF-1 with high affinity, whereas the proximal site binds SF-1 with lower affinities. These findings demonstrate a requirement for SF-1 for human StAR gene expression.

PMID:
9029708
[PubMed - indexed for MEDLINE]
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